Biomedical Engineering Reference
In-Depth Information
Saliva has been used as a biological fluid for the diagnosis and prognosis of periodontal disease
[14]
,
oral cancer
[15
17]
, diabetes
[3]
, and autoimmune disorders
[18]
. In addition, researchers have
identified biomarkers in saliva for the detection of early stage pancreatic cancer
[19]
. Streckfus et al.
[20,21]
measured soluble c-erbB-2 (also known as Her2/neu and is a prognostic breast cancer marker
assayed in tissue biopsies from women diagnosed with malignant tumors) levels in saliva collected
from breast cancer patients and concluded that it may have potential use in the initial detection
and/or follow-up screening to determine the recurrence of breast cancer, thus paving the way towards
personalized medicine.
The barriers to widespread implementation of salivary diagnostics are primarily (a) the lack of
understanding of saliva physiology, most importantly diurnal and circadian variation of molecules
present in saliva; (b) age (age-related variations have emerged, with a particular focus on the pedi-
atric age group), gender, and genetic differences; (c) lack of understanding of the modes of mole-
cule transportation from blood capillaries to saliva; (d) limited functional characterization of
specific salivary peptides and proteins; (e) the fact that many proteins in saliva (i.e., histatins,
statherins, and proline-rich peptides) are highly polymorphic and undergo post-translational modifi-
cations (PTMs) leading to large inter-individual and intra-individual variations
[22]
; (f) the lack of
standardization of appropriate saliva sampling collection methods and proper sampling procedures
with minimal influence on downstream applications
[23,24]
; and (g) the lack of universally
accepted normalization/reference calibrators. Further adding complexity to the above-mentioned
challenges is the reality that the composition of saliva can change based on diet and fluid intake
[25]
. It is important to minimize these variables in a clinical setting by asking participants to refrain
from eating or drinking 1 h prior to donating a saliva sample to obtain similar baseline values
between individuals and to report the salivary analyte/protein concentrations as a function of sali-
vary flow rate.
22.1.2
Saliva production and bimolecular transport
Human saliva is a plasma ultra-filtrate and contains proteins that are either synthesized in situ in
the salivary glands or are derived from blood. Saliva is primarily produced by three major glands
(parotid, submandibular, and sublingual) and about 400 minor glands that are located within the oral
cavity. A healthy adult produces 500
1500 mL of saliva in general per day, at a rate of approxi-
mately 0.5 mL/min
[24]
, but several physiological and pathological conditions can modify saliva
production quantitatively and qualitatively. Smell and taste stimulate saliva production and secretion,
as do chewing, psychological and hormonal status, drugs, age, hereditary influences, oral hygiene,
and physical exercise
[26]
. Also, the composition of saliva may be affected by many physiological
variables
[27]
, of which the most important factors are the salivary flow rate
[28]
, the type of saliva
(e.g., stimulated versus unstimulated), genetic polymorphisms
[29]
, nature and duration of the stimu-
lus, and circadian and circannular rhythms
[30,31]
. As an example, salivary cortisol levels are high-
est in the morning, soon after awakening and lowest in the evening and at night, and one should take
this factor into consideration when interpreting salivary cortisol measurements
[32,33]
.
Salivary glands are made up of two types of epithelial cells, and these are acinar and ductal
cells. Saliva is produced in the acinar cells and stored in the salivary granules until an appropriate
stimulation occurs. Upon stimulation, the salivary fluid passes from the lumen of the acinar cells to
a branching network of ducts, where it is collected and enters into the oral cavity. Upon release
